This is an open label study for any patients with a bile duct cancer or gallbladder cancer, who will be treated with gemcitabine and cisplatin chemotherapy (the ABC02 regime). Patients recruited onto this study will have a reduction of their hydration time and be given Akynzeo as an anti-sickness drug, to assess tolerability compared to the current standard of care. The aim of this research is to assess the tolerability of a shorter hydration time, which may improve patient satisfaction as they would then spend less time in hospital having chemotherapy, saving both time and money for the institutions also.

The ABC02 treatment regime was established in 2010 following publication in the New England Journal of Medicine and has since become the standard of care treatment of bile duct cancers otherwise known as cholangiocarcinomas, as well as gallbladder cancer. The treatment consists of gemcitabine and cisplatin given synergistically. This combination has been shown to yield an overall survival advantage of 3.6 months compared to when gemcitabine is given on its own, with additional improvements in performance status and tumour control in patients.

Currently, the ABC02 regime includes a long hydration schedule based on previous use of high doses of cisplatin and perhaps historically the lack of efficacious antiemetics. Cisplatin is often associated with severe nausea and vomiting that lead to dehydration. In fact, cisplatin is a direct nephrotoxin, owing to its pro-inflammatory action in the kidneys and being able to cause immediate vasoconstriction of renal microvasculature on administration, and this coupled with its effect to induce dehydration due to nausea and vomiting, prevented the inclusion of cisplatin into many combinational regimens. 50% of patients in initial studies were found to suffer from nephrotoxicity on cisplatin and thus the administration of intravenous saline to combat this effect by inducing diuresis has also been standard of care when giving cisplatin chemotherapy. However, it is still not known what the optimal hydration solution and procedure are as there are no studies comparing either of these factors.

Akynzeo is a mixture of both a 5HT3 blocker palonosetron and a neurokinin 1 inhibitor netupitant. Together the drugs are able to combat nausea and vomiting during the acute phase and delayed phase after chemotherapy. The introduction of 5HT3 blockers cut the incidence of acute nausea and vomiting in chemotherapy patients considerably, but in fear of the historical nephrotoxicity, copious volumes of IV saline remains part of the regime. This entire procedure takes 8 hours for delivery and risks fluid overload often requiring diuretic management.

For reference: gemcitabine is an antimetabolite and works by imitating a pyrimidine and replacing the cytidine in nucleic acid during DNA replication. By doing so, gemcitabine halts tumour growth as actual nucleosides cannot be attached to this faulty nucleoside and this results in apoptosis. Cisplatin on the other hand is an alkylating agent and kills cancer cells by binding to DNA and interfering with its repair mechanism; upon binding to DNA it further attracts other DNA repair proteins to irreversibly bind to the structure distorting its shape and inducing apoptosis.

Inclusion Criteria:

• Adults with normal renal function at the start i.e. eGFR>60, Performance status 0 and 1, controlled nausea and vomiting at baseline.
• ECOG performance status 0 or 1
• Diagnosed with either cholangio carcinoma, gallbladder cancer, pulmonary cancer or pancreatic cancer. Patients should be able to tolerate 1 litre of oral fluid pre-treatment and post treatment.
• Decision to treat with the gemcitabine and cisplatin used in the ABC02 trial.

Exclusion Criteria:

• Participants under the age of 18 years old with Chronic renal impairment. The standard exclusion of renal impairment for cisplatin implies that this study would not be offered to patients, who can't be safely offered cisplatin
• Uncontrolled nausea or vomiting
• Unable to drink 1 litre of fluid